La Jolla,
California
92093
Purpose:
RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing
so they stop growing or die. Combining more than one drug may kill more cancer cells.
PURPOSE: Phase II trial to study the effectiveness of combination chemotherapy in treating
patients who have non-Hodgkin's lymphoma or acute lymphocytic leukemia.
Study summary:
OBJECTIVES:
- Determine if increasing the methotrexate dose in combination with standard treatment is
feasible in patients with advanced small noncleaved cell non-Hodgkin's lymphoma or
B-cell acute lymphocytic leukemia.
- Assess the toxicity of this intensified therapy in these patients.
- Assess the feasibility of treating these patients that have CNS disease at diagnosis
with this intensified therapy plus etoposide and ifosfamide.
- Assess toxicities and late effects of this intensive therapy on the central nervous
system, cardiac function, and fertility in these patients.
OUTLINE: This is a multicenter study. Patients are stratified according to stage and disease
(stage III non-Hodgkin's lymphoma (NHL) vs stage IV NHL with no CNS involvement vs stage IV
NHL with CNS involvement vs B-cell acute lymphocytic leukemia (B-ALL) with no CNS
involvement vs B-ALL with CNS involvement).
Patients receive methotrexate and cytarabine intrathecally on days 1, 4, 11, and 36 (on day
40 for patients with stage IV NHL or B-ALL only) in combination with alternating courses of:
A) cyclophosphamide IV every 12 hours for a total of six doses on days 1-3, doxorubicin IV
over 30 minutes on day 4, vincristine IV on days 4 and 11, dexamethasone IV or orally twice
daily on days 1-5, and filgrastim (G-CSF) subcutaneously (SQ) or IV over 30 minutes
beginning on day 5 and continuing until blood counts recover and B) methotrexate IV over 24
hours on day 18, methotrexate intrathecally on day 18, dexamethasone IV or orally twice
daily on days 18-22, leucovorin calcium IV or orally every 6 hours for a total of 6 doses on
days 20-21, cytarabine IV over 48 hours on days 20-21, and G-CSF SQ or IV over 30 minutes
beginning on day 22 and continuing until blood counts recover. Patients with stage III NHL
receive at total of 5 courses of treatment (A-B-A-B-A) and patients with stage IV NHL or
B-ALL with no CNS involvement receive a total of 6 courses of treatment (A-B-A-B-A-B).
Patients with CNS involvement receive a third course of treatment: C) etoposide IV over 1
hour on days 36-40, ifosfamide IV over 1 hour on days 36-40, oral dexamethasone twice daily
on days 36-40, and G-CSF SQ or IV over 30 minutes beginning on day 41 and continuing until
blood counts recover. Patients with CNS involvement receive a total of 7 courses of
treatment (A-B-C-A-B-A-B).
Patients are followed every 6 months for 4 years and then annually thereafter.
PROJECTED ACCRUAL: A total of 27-80 patients will be accrued for this study over 24 months.
Criteria:
DISEASE CHARACTERISTICS:
- One of the following diagnoses:
- Histologically confirmed small noncleaved cell non-Hodgkin's lymphoma
- Stage III or IV
- Burkitt's or non-Burkitt's by the Working Formulation OR
- Burkitt's or Burkitt's-like by the REAL classification
- Histologically confirmed B-cell acute lymphocytic leukemia
- At least 25% blasts in bone marrow
- FAB L3 morphology
- FAB L1 morphology allowed if blasts show B-cell markers (CD19, 20, 22) and
surface immunoglobulin positivity
- Must be registered on POG-9900 in past 8 days
PATIENT CHARACTERISTICS:
Age:
- Under 22 at time of diagnosis
Performance status:
- Not specified
Life expectancy:
- Not specified
Hematopoietic:
- Not specified
Hepatic:
- Not specified
Renal:
- Not specified
Other:
- Not pregnant or nursing
- Negative pregnancy test
- HIV positive allowed
PRIOR CONCURRENT THERAPY:
Biologic therapy:
- Not specified
Chemotherapy:
- Not specified
Endocrine therapy:
- No concurrent use of dexamethasone as antiemetic
Radiotherapy:
- Not specified
Surgery:
- Prior surgery allowed
Other:
- No prior therapy except surgery